Suspected North Carolina counterfeit pill-involved deaths, 2020-2022.

The NC Office of the Chief Medical Examiner regularly assumes jurisdiction over deaths that are suspicious, unusual or unattended by a medical professional. In recent years, the presence of counterfeit pills is occasionally suggested by investigatory notes and/or scene findings that document reported consumption of prescription drugs, or prescription drugs on scene, which are not reflected in the final autopsy findings after toxicological analysis of the decedent's blood samples. Counterfeit pill consumption is a major public health hazard worthy of attention from the forensic toxicology community. Seventy-five cases from January 2020 to December 2022 serve as a convenience sample of cases where prescription pills including formulations of alprazolam, oxycodone and hydrocodone were specifically referenced during the death scene investigation as recently consumed, yet an unexpected substance was found during toxicological analysis rather than the expected pharmaceutical drug. Of note, novel benzodiazepines detected included flualprazolam, etizolam, clonazolam metabolite (8-aminoclonazolam), bromazolam, flubromazolam and desalkylflurazepam. Decedents' ages ranged from 16 to 69, across 33 different NC counties. Case notes indicated that eight of the decedents obtained pills through direct personal relationships, six decedents obtained them from "the street" and one decedent likely purchased pills online. Pills were largely consumed orally or through insufflation. Seven case reports contained indication that decedents knew or suspected the counterfeit nature of their pills. This study describes the context and characteristics of 2020-2022 suspected counterfeit pill-involved deaths in NC to further the understanding of the forensic science community, law enforcement partners, public health stakeholders and those potentially at risk through the consumption of counterfeit pills.

Successful de-implementation of an ineffective practice: The fall of docusate.

BACKGROUND: Reducing wasteful practices optimizes value in medicine. Docusate lacks treatment efficacy yet is widely prescribed. This quality improvement project aimed to de-implement docusate in place of a new evidence-based order set. METHODS: This is an ambidirectional study of inpatient laxative orders from 2018 to 2022 â€‹at one institution. We stratified docusate data by service/unit to target prospective deimplementation initiatives. A new evidence-based constipation order set was embedded in Cerner. RESULTS: There were 701,732 docusate orders across 75 services on 68 units. Top docusate ordering services were Trauma, Obstetrics and Hospitalist. Docusate administration rates were higher than for other laxatives. Our efforts reduced docusate orders by 44% over 4 months. PEG and senna orders increased by 58% and 35%. CONCLUSION: Docusate has no efficacy yet is widely prescribed. A structured de-implementation strategy can drive systematic change by leveraging technology and applying multidisciplinary improvement efforts. Our work removed docusate from the inpatient formulary.

Endocarditis, drug use and biological sex: A statewide analysis comparing sex differences in drug use-associated infective endocarditis with other drug-related harms.

OBJECTIVES: Hospitalizations for drug use-associated infective endocarditis (DUA-IE) have risen sharply across the United States over the past decade. The sex composition of DUA-IE remains less clear, and studies have indicated a possible shift to more females. We aimed to compare more recent statewide hospitalization rates for DUA-IE in females versus males and contextualize them among other drug-related harms in North Carolina (NC). METHODS: This study was a retrospective analysis using public health datasets of all NC hospital discharges for infective endocarditis from 2016 to 2020. Drug use-related hospitalizations were identified using ICD-10-CM codes. Discharge rates by year and sex for DUA-IE and non-DUA-IE were calculated and compared to fatal overdoses and acute hepatitis C (HCV). Temporal, demographic, and pregnancy trends were also assessed. RESULTS: Hospitalizations rates for DUA-IE were 9.7 per 100,000 over the five-year period, and 1.2 times higher among females than males. Females composed 57% of DUA-IE hospitalizations over the period. Conversely, fatal overdose, acute HCV, and non-DUA-IE hospitalization rates were higher among males. Age, county of residence, and pregnancy status did not explain the higher DUA-IE among females. CONCLUSION: Females now comprise the majority of DUA-IE hospitalizations in NC, unlike other drug-related harms. No clear demographic or geographic associations were found, and further research is needed to explain this phenomenon. Preventing invasive infections among females who inject drugs should be prioritized.

Tying Overdose Data to Action: North Carolina's Opioid and Substance Use Action Plan Data Dashboard.

From 2000 to 2020, more than 28 000 North Carolina (NC) residents died of drug overdose. In response, NC Department of Health and Human Services worked with community partners to develop an Opioid and Substance Use Action Plan (OSUAP), now in its third iteration. The NC OSUAP data dashboard brings together data on 15 public health indicators and 16 local actions across 8 strategies. We share innovations in design, data structures, user tasks, and visual elements over 5 years of dashboard development and maintenance, with a special focus and supplemental material covering the technical details and techniques that dashboard design and implementation teams may benefit from.

Racial and ethnic differences and COVID-19 pandemic-related changes in drug overdose deaths in North Carolina.

PURPOSE: To examine racial and ethnic differences and COVID-19 pandemic-related changes in key characteristics of drug overdose deaths in North Carolina. METHODS: We used North Carolina State Unintentional Drug Overdose Reporting System data to describe specific drug-involvement, bystander presence, and naloxone administration for drug overdose deaths by race and ethnicity during pre-COVID-19 (May 2019-February 2020) and COVID-19 periods (March 2020-December 2020). RESULTS: For all racial and ethnic groups, drug overdose death rates and the percentage with fentanyl and alcohol involvement increased from the pre-COVID-19 to COVID-19 period, with fentanyl involvement highest among American Indian and Alaska Native (82.2%) and Hispanic (81.4%) individuals and alcohol involvement highest among Hispanic individuals (41.2%) during the COVID-19 period. Cocaine involvement remained high among Black non-Hispanic individuals (60.2%) and increased among American Indian and Alaska Native individuals (50.6%). There was an increase in the percentage of deaths with a bystander present from the pre-COVID-19 to COVID-19 period for all racial and ethnic groups, with more than half having a bystander present during the COVID-19 period. There was a decrease in the percentage of naloxone administered for most racial and ethnic groups, with the lowest percentage among Black non-Hispanic individuals (22.7%). CONCLUSIONS: Efforts to address increasing inequities in drug overdose deaths, including expanded community naloxone access, are needed.

Differences in overdose deaths by intent: Unintentional & suicide drug poisonings in North Carolina, 2015-2019.

Comprehensive fatal overdose prevention requires an understanding of the fundamental causes and context surrounding drug overdose. Using a social determinants of health (SDOH) framework, this descriptive study examined unintentional and self-inflicted (i.e., suicide) overdose deaths in North Carolina (NC), focusing on specific drug involvement and contextual factors. Unintentional and suicide overdose deaths were identified using 2015-2019 NC death certificate data. Specific drug involvement was assessed by searching literal text fields for drug mentions. County-level contextual factors were obtained from NC Institute of Medicine and County Health Rankings, encompassing five SDOH domains (economic stability, social/community context, health care access/quality, education access/quality, neighborhood/built environment). Descriptive statistics were calculated by intent for drug involvement and a variety of contextual factors. During 2015-2019, 9% of NC drug overdose deaths were self-inflicted and 89% were unintentional (2% other/undetermined). Unintentional overdoses largely involved illicit drugs [fentanyl (47%), cocaine (33%), heroin (29%)]. Suicide overdoses frequently involved prescription opioids [oxycodone (18%), hydrocodone (10%)] and antidepressants (32%). Overall, overdose deaths tended to occur in under-resourced counties across all SDOH domains, though unintentional overdoses occurred more often among residents of under-resourced counties than suicide overdoses, with differences most pronounced for economic stability-related factors. There are notable distinctions between unintentional and suicide overdose deaths in demographics and drug involvement, though the assessment of SDOH demonstrated that overdose mortality is broadly associated with marginalization across all domains. These findings highlight the value of allocating resources to prevention and intervention approaches that target upstream causes of overdose (e.g., housing first, violence prevention programs).

The Societal Cost of Excessive Drinking in North Carolina, 2017.

BACKGROUND Excessive drinking, including binge and heavy drinking, is a leading cause of morbidity and mortality in North Carolina. In 2010, excessive drinking cost North Carolina $7.03 billion, and this analysis aimed to update this figure for 2017.METHODS Following the methods of Sacks, et al. (2015), we obtained proxies for the 2010 and 2017 incidence and price for 26 alcohol-attributable cost components. We then multiplied each component's 2010 cost by the incidence trend (2017 incidence/2010 incidence) and price trend (2017 price/2010 price) to estimate the 2017 cost. Finally, we summed these cost components to calculate the total cost and allocated them by payer and county.RESULTS Excessive drinking cost $9.72 billion in North Carolina in 2017, which equals approximately $2.09 per standard drink. Government paid $4.43 billion (45.6%), drinkers paid $3.76 billion (38.7%), and persons other than the drinker paid $1.53 billion (15.7%).LIMITATIONS These methods relied on alcohol-attributable fractions, which were calculated using scientific literature and national data. If consumption patterns differ between the United States and North Carolina, these fractions may not generalize. Scaling processes may over- or underestimate individual cost components, so total state costs should be interpreted as estimates.CONCLUSIONS The societal costs from excessive drinking are high but spread across public sectors. This can make it difficult to attribute this burden to alcohol. While drinkers paid less than half of the costs of excessive drinking, a broad range of stakeholders bore the burden. Evidence-based strategies to reduce excessive drinking may decrease these costs.

Limb-Girdle Muscular Dystrophy R9 due to a Novel Complex Insertion/Duplication Variant in FKRP Gene.

Limb-girdle muscular dystrophy R9 (LGMD2I, LGMDR9) is an autosomal recessive disorder caused by pathogenic variants in the fukutin-related protein (FKRP) gene. We describe a 17 year old boy with LGMDR9 whose symptoms began at age 5 years. Muscle histopathology, immunostaining, and western blotting were consistent with a dystroglycanopathy. Genetic testing identified maternal inheritance of the most common pathogenic FKRP variant c.826C>A (p.L276I). Also detected was a novel insertion and duplication on the paternally inherited FKRP allele: a single nucleotide insertion (c.948_949insC) and an eighteen nucleotide duplication (c.999_1017dup18) predicted to result in premature translation termination (p.E389*). Based on the clinical features and course of the patient, heterozygosity for the common pathogenic FKRP variant, and abnormal glycosylation of alpha-dystroglycan, we suggest that the novel FKRP insertion and duplication are pathogenic. This case expands the genetic heterogeneity of LGMDR9 and emphasize the importance of muscle biopsy for precise diagnosis.

Mental health emergency department visits: An exploration of case definitions in North Carolina.

BACKGROUND: Mental health (MH) disorders comprise a high disease burden and have long-lasting impacts. To improve MH, it is important to define public health MH surveillance. METHODS: We compared MH related definitions using ICD-10-CM codes: The Council of State and Territorial Epidemiologists' (CSTE) surveillance indicators for all MH, mood or depressive, schizophrenic, and drug/alcohol-induced disorders; and North Carolina's (NC) syndromic surveillance system's definition for anxiety/mood/psychotic disorders, and suicide/self-harm. We compared code definitions and frequent codes in 2019 emergency department (ED) data for those age ≥ 10 years. RESULTS: CSTE's definition resulted in over one million MH-related visits (23% of all ED visits) and NC's definitions in 451,807 MH-related visits (9% of all ED visits). Using CSTE's broadest definition, nicotine use was the most common visit type; using NC's definitions, it was major depressive disorder. CONCLUSIONS: Standardizing population-level MH indicators benefits surveillance efforts. Given its prevalence, efforts should focus on documenting MH to improve treatment and prevention.

Differences in Mortality Among Infants With Neonatal Opioid Withdrawal Syndrome.

INTRODUCTION: Prior studies are mixed regarding whether infants diagnosed with neonatal opioid withdrawal syndrome have a higher risk of mortality than other infants. However, these studies have not accounted for whether mothers of infants with neonatal opioid withdrawal syndrome received medication for opioid use disorder in pregnancy. METHODS: Linked data from 2016‒2018 North Carolina birth certificates, maternal and infant Medicaid claims, and infant death certificates were analyzed in summer 2021 to compare mortality and causes of mortality before age 1 year among infants diagnosed with neonatal opioid withdrawal syndrome whose mothers did and did not have claims for medication for opioid use disorder in pregnancy (N=4,480). RESULTS: Compared with mothers with medication for opioid use disorder claims in pregnancy (45.5%), mothers without medication for opioid use disorder claims (55.5%) were younger, more likely to be Black non-Hispanic, less likely to have paternity established, and more likely to have no prenatal care. The proportion (1.3%, n=31 vs 1.0%, n=21) and rate (3.5 vs 2.9 deaths per 100,000 infant days) of mortality was higher among infants of mothers without medication for opioid use disorder claims than infants of mothers with medication for opioid use disorder claims. Sudden unexpected infant death syndrome was the primary cause of death for infants of mothers with (90.5%) and without (58.1%) medication for opioid use disorder claims. CONCLUSIONS: Results highlight the importance of assessing for potential differences in outcomes according to whether infants with neonatal opioid withdrawal syndrome were exposed to medication for opioid use disorder. Efforts to ensure equitable access to medication for opioid use disorder and other support services in pregnancy are needed to promote healthy maternal and infant outcomes.

Opioid Overdose Deaths Among Formerly Incarcerated Persons and the General Population: North Carolina, 2000‒2018.

Objectives. To compare opioid overdose death (OOD) rates among formerly incarcerated persons (FIPs) from 2016 to 2018 with the North Carolina population and with OOD rates from 2000 to 2015. Methods. We performed a retrospective cohort study of 259 861 North Carolina FIPs from 2000 to 2018 linked with North Carolina death records. We used indirectly standardized OOD mortality rates and ratios and present 95% confidence intervals (CIs). Results. From 2017 to 2018, the OOD rates in the North Carolina general population decreased by 10.1% but increased by 32% among FIPs. During 2016 to 2018, the highest substance-specific OOD rate among FIPs was attributable to synthetic narcotics (mainly fentanyl and its analogs), while OOD rates for other opioids were half or less than that from synthetic narcotics. During 2016 to 2018, the OOD risk for FIPs from synthetic narcotics was 50.3 (95% CI = 30.9, 69.6), 20.2 (95% CI = 17.3, 23.2), and 18.2 (95% CI = 15.9, 20.5) times as high as that for the North Carolina population at 2-week, 1-year, and complete follow-up after release, respectively. Conclusions. While nationwide OOD rates declined from 2017 to 2018, OOD rates among North Carolina FIPs increased by about a third, largely from fentanyl and its analogs. (Am J Public Health. 2022;112(2):300-303. https://doi.org/10.2105/AJPH.2021.306621).

The Impact of the COVID-19 Pandemic on Disparities in Motor Vehicle Traffic Deaths and Injuries among North Carolina American Indians.

A Periodic Feature to Inform North Carolina Health Care Professionals About Current Topics in Health Statistics.

An organoid-based screen for epigenetic inhibitors that stimulate antigen presentation and potentiate T-cell-mediated cytotoxicity.

In breast cancer, genetic heterogeneity, the lack of actionable targets and immune evasion all contribute to the limited clinical response rates to immune checkpoint blockade therapy. Here, we report a high-throughput screen based on the functional interaction of mouse- or patient-derived breast tumour organoids and tumour-specific cytotoxic T cells for the identification of epigenetic inhibitors that promote antigen presentation and potentiate T-cell-mediated cytotoxicity. We show that the epigenetic inhibitors GSK-LSD1, CUDC-101 and BML-210, identified by the screen, display antitumour activities in orthotopic mammary tumours in mice, that they upregulate antigen presentation mediated by the major histocompatibility complex class I on breast tumour cells and that treatment with BML-210 substantially sensitized breast tumours to the inhibitor of the checkpoint programmed death-1. Standardized measurements of tumour-cell killing activity facilitated by tumour-organoid-T-cell screens may help with the identification of candidate immunotherapeutics for a range of cancers.

Literal text analysis of poly-class and polydrug overdose deaths in North Carolina, 2015-2019.

BACKGROUND: The literal text on death certificates was leveraged to enhance the examination of trends in the specific drugs and drug combinations involved in North Carolina (NC) overdose deaths from 2015 to 2019. METHODS: Using NC death certificate data, overdose deaths included those with a drug poisoning as the underlying ICD-10 cause-of-death code (n = 10,117). The literal text from three death certificate fields were searched for drug mentions by integrating a tool developed by the Council of State and Territorial Epidemiologists Overdose Subcommittee with search terms originating from a National Center for Health Statistics/Food and Drug Administration collaboration. Descriptive statistics were calculated to evaluate substance classes, specific drugs, and drug combinations most frequently involved in these deaths over time. RESULTS: From 2015-2019, polydrug involvement in NC overdose deaths increased (71% in 2015 to 75% in 2019). During the study period, opioid involvement shifted from heroin and/or oxycodone in 2015 to predominantly fentanyl in 2019, with fentanyl involvement increasing from 15% to 58%. Psychostimulant involvement increased for both cocaine (2015: 21%, 2019: 35%) and methamphetamine (2015: 3%, 2019: 13%). Benzodiazepine involvement, including alprazolam and clonazepam, declined during the study period, while the involvement of alcohol and antiepileptics/sedative-hypnotics, specifically gabapentin, remained stable. The top polydrug combinations in 2019 were fentanyl + cocaine (15% of all overdose deaths), fentanyl + heroin (10%), fentanyl + cocaine + heroin (6%), and fentanyl + methamphetamine (4%). CONCLUSIONS: Incorporation of literal text methodology into ongoing overdose surveillance can facilitate the identification of specific, emerging drugs and combinations and inform targeted overdose prevention approaches.

Prenatal Use of Medication for Opioid Use Disorder and Other Prescription Opioids in Cases of Neonatal Opioid Withdrawal Syndrome: North Carolina Medicaid, 2016-2018.

Objectives. To estimate use of medication for opioid use disorder (MOUD) and prescription opioids in pregnancy among mothers of infants with neonatal opioid withdrawal syndrome (NOWS). Methods. We used linked 2016-2018 North Carolina birth certificate and newborn and maternal Medicaid claims data to identify infants with an NOWS diagnosis and maternal claims for MOUD and prescription opioids in pregnancy (n = 3395). Results. Among mothers of infants with NOWS, 38.6% had a claim for MOUD only, 14.3% had a claim for prescription opioids only, 8.1% had a claim for both MOUD and prescription opioids, and 39.1% did not have a claim for MOUD or prescription opioids in pregnancy. Non-Hispanic Black women were less likely to have a claim for MOUD than non-Hispanic White women. The percentage of infants born full term and normal birth weight was highest among women with MOUD or both MOUD and prescription opioid claims. Conclusions. In the 2016-2018 NC Medicaid population, 60% of mothers of infants with NOWS had MOUD or prescription opioid claims in pregnancy, underscoring the extent to which cases of NOWS may be a result of medically appropriate opioid use in pregnancy.

Effect of Hearing Aid Technology Level and Individual Characteristics on Listener Outcome Measures.

Purpose The purpose of the study was to determine the effect of hearing aid technology level on listener outcome measures. In addition, we aimed to determine if individual characteristics such as noise acceptance and the demands of the listening environment impacted performance and preference. Method A repeated-measures, single-blinded research design was utilized. Twenty-four adults recruited by mail from The University of Tennessee Health Science Center Audiology Clinic participated in this experiment (15 men and nine women). Participants completed two 2-week trial periods using Unitron T Moxi Fit FLEX:TRIAL devices programmed as basic or premium technology levels. A data-logging feature, Log It All (LIA), quantified the demands of the listening environment. At the end of each trial, outcome measures were obtained using Pascoe's High-Frequency Word List, the Hearing in Noise Test, the Quick Speech-in-Noise Test, the Acceptable Noise Level (ANL), the Speech, Spatial and Qualities of Hearing short form, satisfaction ratings, and preference. Results Results for ANL, satisfaction in large groups, and LIA total coverage were significantly improved for the premium devices. Participants who preferred the premium devices received significant improvement with premium devices on the ANL and the speech in small group and speech in large group satisfaction ratings, whereas participants who preferred the basic devices did not receive significant improvement with premium devices on any outcome measure. Participants in more demanding listening environments received significant improvement with premium devices on the ANL, whereas participants in less demanding listening environments did not receive significant improvement with premium devices on any outcome measure. Conclusions Group data revealed similar outcomes between technology levels on most measures; however, noise acceptance and satisfaction for speech in a large group were significantly improved when using the premium devices. Individual characteristics such as noise acceptance and listening demands may be useful when comparing hearing aid technology levels for a given patient.